Cerebral Resuscitation following cardiac arrest is the focus of many intense controversies. The role of the impaired reperfusion phenomenon in the development of continuing cerebral damage after total cerebral ischemia (TCI) remains unclear. This cerebral vasospasm seen post-TCI has been shown in this laboratory to be similar in both dogs and primates. Using a double occlusion balloon model for TCI developed in this laboratory and radiolabelled microspheres for sequential measurement of regional cerebral blood flow (RCBF), we have evaluated the effect of various pharmacological interventions on both RCBF after TCI and on chronic neurological outcome (nitroprusside, thiopental, nifedipine, indomethacin and 1-Benzyl Imidazole). Over the next 3 years, we plan to conduct multi-disciplinary studies on the basis mechanisms of cerebral damage following TCI, employing new techniques to monitor cerebral oxidative metabolism (reflectance spectrophotometry), glucose metabolism (3-deoxyglucose autoradiography), neurotransmitter stores/enzymatic activities, and RCBF (microspheres). Pharmacological tools will be used to "dissect" the mechanism of continuing cerebral damage (thromboxane synethetase inhibitors, calcium ionophore antagonists, prostacyclin, adenyl cyclase stimulation, opiate antagonists) and hopefully provide a rational basis for future clinical protocols for cerebral resuscitation.